JP2023511485A - Sample holder and sample holder handling system for performing X-ray analysis on crystalline samples - Google Patents

Abstract

A sample holder (3) for performing X-ray analysis on a crystalline sample (11) includes a mounting support with a first end attachable to a goniometer head, with a predetermined The crystalline sample (11) can be attached to the mounting support at a distance of . The sample holder (3) further comprises a holder base provided at a first end of the mounting support with means for mounting said holder base to the goniometer head, said holder base being adapted to fit the wells of the well plate (1). 2). The holder base includes a ferromagnetic material for mounting the holder base to a magnetic base element provided on or within the goniometer head. The mounting support comprises a tube, preferably made of glass, into which the crystalline sample (11) can be inserted. The sample holder (3) may also include a base disc (14), which after insertion of the sample holder (3) into the wells (2) of the wells (2) of the well plate (1). Provide a lid for The holder base may include a holder ring (7), which is arranged at the first end of the mount support and circumferentially surrounds the mount support. A base disc (14) is adapted to be removably attached to the holder ring (7). A crystalline sponge is attached to the mounting support.

Description

The present invention is a sample holder for performing X-ray analysis on a crystalline sample, said sample holder comprising a mounting support having a first end attachable to a goniometer head, said first The present invention relates to a type in which the crystalline sample can be attached to the mount support with a predetermined distance from the edge.

X-ray crystallography is well known for determining the atomic and molecular structure of crystals. In this method, the crystal atoms diffract a beam of incident X-rays into many specific directions. By measuring the angles and intensities of these diffracted beams, a three-dimensional image of the electron density inside the crystal can be obtained. Based on this electron density, other characteristic features of the liquid crystal structure can be determined, such as the average position of atoms within the crystal, as well as their chemical bonding, their disorder, and various other information.

For single crystal X-ray diffraction measurements (sc-XRD), the crystal is mounted on a goniometer. A goniometer is used to position the crystal in a selected orientation. For each of the different orientations, the crystal is illuminated with a highly focused monochromatic beam of X-rays, producing a diffraction pattern consisting of regularly spaced spots known as reflections. Two-dimensional images taken at different orientations are transformed into a three-dimensional model of the electron density inside the crystal using a mathematical Fourier transform method combined with known chemical data about the sample.

Other techniques such as infrared spectroscopy, nuclear magnetic resonance, or mass spectroscopy can provide indirect information. Interpretation of this information typically requires a high degree of expertise and expert experience. In most cases, the structure of a species cannot be determined by applying a single technique, requiring a combination of different analytical tests. This makes the process time long and expensive.

However, sc-XRD requires single crystals of at least a given size, quality and shape to yield sufficiently high diffraction intensities. In many cases, this crystal must be grown using techniques such as slow cooling or vapor phase diffusion. The crystal must be mounted and aligned on the goniometer so that it rotates in different orientations within the highly focused X-ray beam. Depending on the size and quality of the crystals, measurements typically last from hours to days. Based on intense X-ray irradiation, the measurements are performed at low temperatures, for example using a liquid nitrogen cooling system to prevent the crystals from being damaged during the measurements.

Therefore, current single crystal X-ray structure determination procedures require a series of preparatory steps for handling crystalline samples before and during measurements. These preparatory steps have to be performed manually in most cases. In the case of current state-of-the-art technology, suitable crystals are selected from a large number of crystals under a microscope or binoculars. A selected crystal is fixed to the tip of a suitable sample holder, usually using a small amount of oil. The oil serves both as a protector during long measurement times as well as an adhesive to hold the crystal in place during X-ray measurements at low temperatures. Another preparation procedure is characterized by gluing the crystal on top of a fiber of amorphous material or within a small diameter tube, typically of amorphous material such as glass or polyimide. Such tubes are typically closed after insertion of the crystalline sample to seal the sample.

The sample holder is then placed on the X-ray goniometer, for example by manually fixing the sample holder onto a brass pin or a magnetic goniometer head.

It is also known to use crystalline sponges for smooth structure elucidation of small molecules. Crystalline sponges are formed from porous composites. This composite is characterized by wide pores with typical dimensions of a few angstroms, eg, 1 nm to 0.1 nm. An analyte can be immersed in the pores. Here the analyte is aligned and uniformly oriented with the crystalline sponge structure. This soaked crystalline sponge is then treated like a small molecule single crystal, and in many cases structural analysis by X-ray diffraction is possible. Such crystalline sponges are detailed in WO2014/038220 or WO2016/143872. Like ordinary single crystals, crystalline sponges need to be handled with extra care to avoid breakage.

Current methods of structure elucidation by sc-XRD are very time consuming, primarily requiring careful and careful handling to avoid breakage, loss, or contamination. Moreover, the handling of crystals needs to be done under a microscope, requiring skilled personnel and special equipment such as sample holders and tools for micromanipulation. Many of the required steps cannot currently be automated for a number of reasons. Crystals are typically transparent and colorless and thus feature low contrast, making camera-assisted handling difficult. This is because software detection of the crystal circumference is not possible, especially for small crystals. Furthermore, the crystals must be collected from containers such as crystallization vials, adding an additional level of non-uniform optical background, further hindering camera-assisted handling.

Also, current mounting methods can fail for a variety of reasons. In some cases, there is an incompatibility of reagents, such as adhesives or oils, applied to mount the crystalline sample onto the sample holder. Unwanted movement of the crystalline sample during measurement or during transportation or mounting of the sample holder to the goniometer can make analysis of the measured diffraction pattern difficult. Furthermore, the high scattering background from the sample holder combined with the small size of the crystalline sample also degrades the measurement results. In the specific case of the crystalline sponge technique, additional requirements also include immersion of the analyte. In this case, the manually selected crystalline sample must be manually retrieved from the vial to be mounted on the diffractometer. Especially for the application of the crystalline sponge technique, since several steps are required for structure elucidation (immersion, drying and evaporation of solvent, several transfers or loadings of the sample onto the X-ray sample holder), Automation is a big bonus.

SUMMARY OF THE INVENTION It is therefore an object of the present invention to provide a sample holder for performing X-ray analysis on crystalline samples, which facilitates handling of the crystalline sample during the preparation of the X-ray measurements as well as during the execution of the X-ray measurements. , to provide a sample holder. The sample holder preferably allows secure mounting and positioning of the crystalline sample without significantly increasing the interference of the X-ray measurements by the sample holder.

According to the invention, the sample holder comprises a holder base provided at a first end of the mounting support with means for mounting the holder base to the goniometer head, the holder base comprising a well plate are shaped to fit into the wells of the The means for mounting the holder base to the goniometer head may include a shape of the holder base that is configured to and facilitates fixing the holder base on the goniometer head. For example, the holder base may present a notch or recess that allows positive locking of the holder base onto the goniometer head. The holder base can also be configured to be inserted into a clamping system located on the goniometer head. The holder base is further shaped to allow the sample holder to be inserted into the wells of the well plate. The dimensions and shape of the holder base and mounting support are adapted to the dimensions of the well such that the sample holder can be inserted into the well by locating the mounting support inside the well, thereby removing the well. Close the opening with the holder base. The holder base can be used as a lid. The lid allows closure of the well and protects the mounting support and crystalline sample. A crystalline sample is attached to the mounting support and placed inside the well. The rear side of the holder base is accessible from the outside of the well plate and can be used for automated handling systems, for example. An automated handling system withdraws the sample holder from the wells of the well plate and then transfers and attaches the sample holder to the goniometer head.

In a preferred embodiment of the invention said holder base comprises a ferromagnetic material for mounting said holder base to a magnetic base element provided on said goniometer head or provided inside said goniometer head. The ferromagnetic material may be a part or component made of ferromagnetic material located inside the holder base or attached to the outside of the holder base. A holder base comprising a ferromagnetic material can be snapped onto the magnets commonly used on goniometer heads, thus providing a defined position and secure clamping of the sample holder onto the goniometer head.

In another aspect of the invention, the mounting support comprises a tube into which the crystalline sample can be inserted. The tube may be made of glass or of a suitable polymer that does not cause significant scattering, thus reducing the interference of the X-ray radiation and possible disruption of the measurement results of X-ray diffraction measurements. Furthermore, the wall thickness of the tube may be small, for example 0.02 mm or less. Nevertheless, the tube surrounds the crystalline sample inserted into the tube and allows reliable positioning and mechanical protection of the crystalline sample when handling the sample or performing measurements on the sample.

Advantageously, the tube is made of a material that is solvent resistant to the fluids commonly used for sample preparation and for attaching crystalline samples to mounting supports. This prevents unwanted contamination or deterioration of the crystalline sample before or during the measurement.

In another aspect of the invention, the sample holder includes a base disk, which provides a lid for the wells of the well plate after insertion of the sample holder into the wells. The diameter of the base disk can match the diameter of the well opening. This diameter allows the insertion of the base disc into the opening of the well. This results in a positive closure of the well and thus protects the mounting support with the crystalline sample attached to the well located inside the well. Such a base disc may be part of a holder base configured to be inserted into wells of a well plate. It is also possible to combine the holder base with the base disc. The base disc is larger than the well openings of the well plate and sits on top of the surface of the well plate when the mounting support is placed inside the wells. Preferably, such base disk has a diameter slightly larger than the diameter of the well opening. The perimeter of the well openings provides a circular seat for the base disc on the surface of the well plate.

According to an advantageous embodiment of the invention, said holder base comprises a holder ring, said holder ring being arranged at a first end of said mount support and surrounding said mount support in the circumferential direction. The shape of the holder ring can conform to the shape of the well cavity in the well plate adjacent the well opening, thus allowing the holder ring to be inserted into the well and adjacent the well opening. provide a fixed position for the holder ring The mounting support protruding from the holder ring is then directed towards the bottom of the well and is securely positioned inside the well. The holder ring also provides mechanical or magnetic features. This feature allows easy handling of the sample holder with a suitable automatic handling system before or during the measurement.

In another aspect of the invention, said base disc is removably attached to a holder ring. The holder ring can be inserted into the wells of the well plate, while the base disc can be shaped to remain on top of the surface of the well plate and allow tight closure of the wells at the well openings. Additionally, the bottom side of the base disc, which is accessible from outside the well, can provide interlocking, clamping or catching means that allow easy handling of the sample holder by automated handling systems.

According to one embodiment of the invention, a crystalline sponge is attached to said mounting support. A pre-assembled sample holder comprising a crystalline sponge attached to a mounting support facilitates the preparation of individual crystalline samples. The only requirement is to add the analyte into the crystalline sponge. This can be easily done by immersing a mounting support comprising a crystalline sponge in a solution containing the crystalline molecules to be analyzed.

According to another embodiment of the invention, said crystalline sponge is arranged inside said tube. The tube surrounds and protects a crystalline sponge positioned inside the tube. A crystalline solution can be introduced into the tube, which in turn soaks the crystalline sponge, introducing crystalline molecules into the porous sponge material. Subsequent closure of the tube preserves the crystalline sample, allowing repeated use and long-term storage between subsequent measurements without any alteration or deterioration of the crystalline sample.

In another aspect of the invention, the specimen holder includes a protective container, the protective container being attached to the mounting support and to the mounting support at a predetermined distance relative to the first end. Contains a crystalline sample that can be formed. The protective container can be detachably coupled with the holder base or can be clamped onto the holder base. Preferably, the protective container comprises a threaded section and can be screwed onto the holder ring or onto the base disc of the sample holder. A protective container surrounds the mounting support and allows for mechanical protection of, for example, a glass tube with a crystalline sample mounted therein. The protective container may consist of any suitable synthetic material. The protective container can be removed prior to performing X-ray measurements, but can be attached to the holder base to protect the crystalline sample during storage and transport of the sample holder inside or outside the wells of the well plate.

The invention also provides a sample holder handling system for performing X-ray analysis on a crystalline sample, comprising a goniometer with a goniometer head, at least one sample holder and a well plate, said sample holder relates to a sample holder handling system formed according to any one of the preceding claims and adapted to the wells of the well plate. A number of sample holders and well plates can be used in studies for structure elucidation by X-ray crystallography. X-ray crystallography will lead to more convenient handling of crystalline samples. Each crystalline sample itself, ie a single crystal or a crystalline sponge, is better protected against environmental influences when stored in the corresponding well of the well plate. For scientists, handling is also improved. This is because the better the sample is protected, the less care is required during handling. Also, the sample holder can be easily attached to the goniometer head, especially compared to the current manual handling of sample holders.

Beyond that, a higher degree of automation becomes possible. Since the sample holder can be routinely and automatically picked up and returned, the crystalline sample can be automatically handled by the automated handling system.

A further degree of automation can be achieved in combination with customized well plates or holder rings that allow the use of commercially available well plates. Well plate formats, typically containing 24 or 96 wells, or large formats of 384 or 1536 wells, are standardized and compatible with all kinds of machines. As such, they are widely used for automation in areas such as sample processing, pipetting, and measurements. Thanks to the invention, the specimen holder can now be processed automatically by the machine. Customization of the well plate forms the well plate to receive multiple sample holders within each well by adding openings or holes to the bottom of each well within the well plate.

In another aspect of the invention, the sample holder includes a base disk having a diameter that matches the diameter of the wells of the well plate. The base disc can include clamping means for engaging the base disc with an automated sample holder manipulation system.

According to another embodiment of the invention, an insert ring is arranged at the bottom of the wells of said well plate, said insert ring supporting a base disc of a sample holder inserted into the well of said well plate. do. By inserting the insert ring into the well, the upper end of the insert ring near the opening of the well serves as a stop for the holder ring or base disc of the sample holder placed inside the well. The insert ring surrounds and encloses the mounting support and the crystalline sample or crystalline sponge attached to the mounting support, thus providing additional protection to the sample. The dimensions of the insert ring, specifically the height of the insert ring, complement the height of the holder ring or base disc so that the combination of the sample holder inside the well and the insert ring is the full height of the well. It is

Further, in accordance with another aspect of the present invention, the holder base includes a holder ring, and the outer diameter and sides of the holder ring are aligned with the wells of the well plate at the top of the wells and near the openings of the wells. is configured to match the diameter and inner surface of the For conical well cavities, the holder ring has a matching conical outer surface. The conical outer surface allows for a close-fitting reception of the holder ring in the upper portion of the well, preferably flush with the surface of the well plate.

According to an advantageous embodiment of the invention, said holder ring comprises clamping means for engaging said holder ring with an automatic sample holder handling system.

In yet another aspect of the invention, the sample holder includes a protective container configured to match the outer diameter, sides, and height of the protective container with the diameter, inner surface, and height of the wells of the well plate. It is

The present invention will be more fully understood, and additional features will become apparent, with reference to the following detailed description and accompanying drawings. The drawings are representative only and do not limit the scope of the claims. Indeed, after reading the following specification and viewing the drawings, it will be apparent to those skilled in the art that various modifications and changes may be made without departing from the inventive concept of the invention. Similar parts shown in the drawings are indicated by the same reference numerals.

FIG. 1 is a three-dimensional schematic showing a standardized well plate with 96 wells arranged in a regular pattern, with in some wells sample holders according to the invention inserted into the corresponding wells. It is a diagram. Figure 2 is a schematic exploded view showing a sample holder with a holder ring configured to be placed inside a customized well of a well plate. Figure 3 is a schematic view of the sample holder together with the well of Figure 2, the sample holder with the holder ring being placed inside the well; FIG. 4 is a schematic exploded view of another embodiment of a sample holder with a holder ring, wherein the holder ring is configured to be placed inside standardized wells of a well plate. Figure 5 is a schematic view of the sample holder together with the well of Figure 4, where the sample holder with the holder ring is placed inside the well. FIG. 6 is another embodiment of a sample holder with a base disk and a pin-like mounting support, wherein the pin-like mounting support is configured to be placed inside standardized wells of a well plate; 1 is a schematic exploded view showing an embodiment; FIG. Figure 7 is a schematic view of the sample holder together with the well of Figure 6, where the sample holder with base disk is placed inside the well; Figure 8 is another embodiment of a sample holder comprising a base disk, a pin-like mounting support, and a surrounding tube, the surrounding tube being configured to be placed inside standardized wells of a well plate; 1 is a schematic exploded view showing an embodiment; FIG. Figure 9 is a schematic view of the sample holder together with the well of Figure 8, with the sample holder with pin-like mounting support and surrounding tube placed inside the well.

A well plate 1 with 96 wells 2 is shown in FIG. Wells 2 are arranged in a regular matrix-like pattern on well plate 1 . The arrangement of wells 2 is consistent with such well plate 1 standards that can be used with many different machines and handling systems.

In some of the wells 2, namely in five of the wells 2 at positions A1 to A5 of the well plate 1 shown in FIG. Different embodiments of the sample holder are further described and shown in FIGS. 2-9. The bottom side 4 of each sample holder 3 is flush with the top surface 5 of the well plate 1 . Only the bottom side 4 of each of the sample holders 3 can be seen in FIG.

In general, the well plate 1 preferably conforms to the dimensions provided by the American National Standards Institute (ANSI) for compatibility with pipetting robots or other automated devices. Current standard dimension descriptions are ANSI/SLAS 1-2004 (installation dimensions), ANSI/SLAS 3-2004 (bottom outer flange dimensions), ANSI/SLAS 4-2004 (well location), and sometimes ANSI/SLAS 2-2004 (height dimension), possibly including ANSI/SLAS 6-2012 (well bottom elevation). The standard dimensions of well plate 1 are 127.76 mm in length and 85.48 mm in width. The well plate 1 is also desirably adjusted to applicable future standardizations for the well plate 1 .

A first embodiment of a sample holder 3 according to the invention is shown in FIGS. In these figures, and further similar figures, a cross-section of the well plate 1 from the left edge of the well plate 1 is shown. However, only the first well 2 is shown, whereas half of the second well 2 is only simulated with dashed lines. The sample holder 3 contains a glass tube 6 . The glass tube 6 may resemble a capillary tube. Capillaries are widely used today in X-ray structure elucidation, for example manufactured by Hilgenberg (Malsfeld, Germany), with a wall thickness of 0.01 mm, a funnel-like opening on one side and a closed end on the other side. It is a model (part number 4007630). The glass tube 6 has a thin wall thickness at the bottom, making it possible to measure the sample directly inside the glass tube in an X-ray diffractometer. Furthermore, the length of the glass tube 6 is formed so as to match the height of the well plate 1 . It is shaped to fit the height of the well plate 1, for example 14 mm, 22 mm or 44 mm, and at the same time to the goniometer setting, i.e. to the top of the goniometer head not shown. . The size range compatible with currently commercially available goniometer heads allows for total glass tube 6 lengths of approximately 22 mm to 32 mm. By using the sample holder 3 with other goniometer heads and goniometer settings, the size of the glass tube 6 can also be increased, for example from 10 mm to 50 mm, 100 mm or 250 mm.

Glass tube 6 of sample holder 3 is surrounded by holder ring 7 . The holder ring 7 further includes features that make it suitable for direct attachment to a goniometer in the X-ray diffractometer described above. These features can include metal rings 8 . The metal ring can be held magnetically by the goniometer head with magnets inside or on top of the goniometer head. The dimensions of the holder ring 7 are those of Rigaku, a commercially available magnetic base support that can be used with currently used base magnetic attachments for goniometer heads, such as Rigaku's goniometer head (Part No. 1013156). Magnetic Base Support Z with Strong Magnet" (Part No. 1013161). Other features for attachment to the goniometer head may also include threads, predetermined diameters in combination with pressure-insensitive materials to mate with or clamp onto the goniometer head.

The dimensions of the holder ring 7 can be different. This requires only a few modifications to the goniometer head to allow mounting. These modifications can include small adaptations to the current design.

The shape of the holder ring 7 is round, i.e. circular. However, the holder ring 7 may also have any other shape, for example a square footprint. The shape of the holder ring 7 is preferably adapted to the wells 2 of the well plate 1 , without sinking too much into the wells 2 and close to the openings of the wells 2 at the top, i.e. at the surface 5 of the well plate 1 . retained. As seen in FIGS. 2 and 3, the wells of well plate 1 are customized to receive sample holders 3 by adding openings 9 into the bottoms 10 of each of wells 2, thus glass tubes. 6 to reach into the body of the well plate 1 through the openings 9 .

By permanently attaching the holder ring 7 to the glass tube 6, the best possible stability can be ensured. Removable attachment of the holder ring 7 to the glass tube 6 can also allow recycling by exchanging the glass tube 6 . However, it is considered a basic requirement that the holder ring 7 does not detach from the glass tube 6 during the measurement.

The holder ring 7 preferably has a circular cross-section and a conical contour. The holder ring 7 consists of polymer. The polymer can adhere to the glass tube 6 . A metal ring 8 is preferably attached to the polymer base of the holder ring 7 as a feature for attachment to the goniometer head. However, it is also possible to attach features directly to the glass tube 6 for attachment to the goniometer head. In one embodiment, a metal ring 8 can be attached to the glass tube 6 .

A crystalline sample 11 is placed inside the glass tube 6 . Crystalline sample 11 may be a single crystal to be used for X-ray diffraction measurements. The crystalline sample 11 may consist of a crystalline sponge soaked with a crystalline solution containing crystalline molecules.

In FIGS. 4 and 5 another embodiment of the sample holder 3 in combination with the standardized well plate 1 is shown. An insert ring 12 is inserted into the well 2 , the insert ring being placed on the bottom 10 of the well 2 . The upper side 13 of the insert ring 12 provides a stop supporting the holder ring 7 of the sample holder 3 . The length of insert ring 12 is formed to completely surround glass tube 6 . The glass tube 6 serves as a mounting support for the crystalline sample 11 inside the glass tube 6 .

A base disk 14 is attached to the holder ring 7 and allows the closure of the glass tube 6 and thus protects the contents of the glass tube 6 , ie the crystalline sample 11 inside the glass tube 6 . The size and shape of the sample holder 3 with the base disc 14 can be formed so that it lies completely inside the wells 2 , the rear side of the base disc 14 being flush with the surface 5 of the well plate 1 . be. However, it is possible and may be advantageous to have the base disc 14 outside the well 2 . This allows easy handling of the sample holder 3 by an automatic sample holder manipulation and handling system.

The base disk 14 preferably seals the glass tube 6 and ensures retention of any material within the glass tube 6, such as organic solvents. A feature for attaching the glass tube 6 to the goniometer head, for example a magnetic material, ie a metal ring 8 , can also be seated on top of said base disc 14 . The base disc 14 may also include threads or a threaded mechanism to ensure a tight seal. Base disk 14 may also include a septum or similar device. A septum or similar device allows material to be transferred through the base disc 14 by temporarily puncturing it.

The sample holder 3 may comprise features for unique identification, such as barcodes, two-dimensional barcodes, QR codes, RFID chips, or other features of this kind. It can be captured and read by machines.

6 and 7 the sample holder 3 comprises a pin-like pole 15 instead of the glass tube 6 of the previous embodiment. A pin-like pole 15 serves as a mounting support for the crystalline sample 11 . A crystalline sample is attached to the free end 16 of a pin-like pole 15 . A pin-like pole 15 is mounted on the base disc 14 . A protective enclosure 17 surrounding and surrounding the pole 15 is removably attached to the base disc 14 . The dimensions and shape of the protective container 17 are such that it can be positioned completely inside the wells 2 of the well plate 1 .

Figures 8 and 9 show yet another embodiment of the invention. Sample holder 3 includes both pin-like pole 15 and glass tube 6 . A glass tube 6 surrounds and surrounds a pin-like pole 15 with a crystalline sample 11 . A crystalline sample is attached to the free end 16 of a pin-like pole 15 . A pin-like pole 15 and a glass tube 6 are attached to the base disc 14 . The base disc also includes a metal ring 8 embedded within the base disc 14 .

EXAMPLES The present invention will be described in more detail and concretely with reference to examples. However, this is not a limitation of the invention.

For proof of concept, a prototype of the sample holder 3 with the glass tube 6 was produced. The prototype included a glass tube 6 made of borosilica glass with a diameter of 0.3 mm and a wall thickness of 0.01 mm. Such glass tubes 6 are commercially available, for example as capillary tubes having a length of several centimeters. The glass tube 6 was melt closed with a flame at a distance of approximately 22 mm measured from the open end of the glass tube 6 .

A glass tube 6 was glued into the holder ring 7 . The holder ring consisted of a short plastic pipe with a length of approximately 9 mm, an outer diameter of 4 mm and an inner diameter of 3 mm. The pre-closed end of the glass tube 6 was hidden inside the holder ring 7, whereas the open end of the glass tube 6 faced outwards. A small metal tube 8 was glued to the top of the holder ring 7, ie to the side of the holder ring 7 where the open end 18 of the glass tube did not face outwards. The metal ring 8 was a shim normally used as a spacer plate for screws with an inner diameter of 3.2 mm and an outer diameter of 7 mm.

For on-going studies, as stated in the publication (M. Hoshino, A. Khutia, H. -Z. Xing, Y. Inokuma, M. Fujita, IUCrJ, 2016, 3, 139-151) was loaded into the glass tube 6 under a microscope. The sample holder 3 loaded with the glass tube 6 was then magnetically attached to the magnetic goniometer head. The diffraction pattern of the crystalline sample 11 inside the crystalline sponge was successfully recorded at a temperature of 200 k and the structure could be successfully solved using standard protocols.

A well plate 1 with a customized design was made according to the following requirements. The well plate included the well plate base dimensions as defined by ANSI. The height was 34 mm. Well 2 itself was round and approximately 9 mm in diameter. The well 2 has a cylindrical shape and is sunk into the well plate 1 by about 9 mm. The bottom 10 of well 2 had a notch in the middle with a diameter of approximately 2 mm.

When the sample holder 3 with the glass tube 6 described above was placed in the customized well plate 1 prototype, the tip of the glass tube 6 could fit in the middle of the well 2 through the notched hole. A sample holder 3 together with a holder ring 7 was placed on the bottom 10 of the wells 2 of the customized well plate 1 .

It has been demonstrated that magnets can be used to remove sample holders 3 from well plate 1 or insert sample holders 3 into wells 2 for storage and transport of sample holders 3 before, between and after measurements. was done.

Claims (18)

A sample holder (3) for performing X-ray analysis on a crystalline sample (11), said sample holder (3) having a mounting support with a first end attachable to a goniometer head. said crystalline specimen (11) may be mounted on said mounting support at a predetermined distance to said first end, said specimen holder (3) being positioned at the first end of said mounting support; At one end it comprises a holder base with means for mounting the holder base to said goniometer head, said holder base being shaped to fit into the wells (2) of the well plate (1). A sample holder (3), characterized in that: Specimen holder (3) according to claim 1, wherein the holder base comprises a ferromagnetic material for mounting the holder base to a magnetic base element provided on the goniometer head or provided inside the goniometer head. . A sample holder (3) according to claim 1, wherein said mounting support comprises a tube into which said crystalline sample (11) can be inserted. 4. The sample holder (3) according to claim 3, wherein said tube is a glass tube (6). Said sample holder (3) comprises a base disc (14), which after insertion of said sample holder (3) into said wells (2) is in said wells (2) of said well plate (1). 2. The sample holder (3) according to claim 1, providing a lid for. A specimen holder according to claim 1, wherein said holder base comprises a holder ring (7), said holder ring being arranged at a first end of said mount support and surrounding said mount support in a circumferential direction. 3). Specimen holder (3) according to claims 5 and 6, wherein the base disc (14) is adapted to be removably attached to the holder ring (7). A sample holder (3) according to claim 1, wherein a crystalline sponge is attached to said mounting support. Sample holder (3) according to claims 3 and 8, wherein the crystalline sponge is arranged inside the tube. Said sample holder (3) comprises a protective container (17), said protective container being attached to said mounting support and to said mounting support at a predetermined distance with respect to said first end. 2. The sample holder (3) according to claim 1, containing a physical sample (11). A sample holder handling system for performing X-ray analysis on a crystalline sample (11), comprising a goniometer with a goniometer head, at least one sample holder (3) and a well plate (1) , the sample holder handling system, wherein the sample holder (3) is formed according to any one of claims 1 to 10 and is adapted to the wells (2) of the well plate (1). 12. A sample holder handling system according to claim 11, wherein the sample holder (3) comprises a base disk (14) having a diameter matching the diameter of the wells (2) of the well plate (1). 13. The sample holder handling system of claim 12, wherein the base disc (14) includes clamping means for engaging the base disc (14) with an automated sample holder handling system. An insert ring (14) was placed in the bottom (10) of the wells (2) of said well plate (1), said insert ring being inserted into the wells (2) of said well plate (1). 13. A sample holder handling system according to claim 12, supporting the base disc (14) of the sample holder (3). The holder base includes a holder ring (7), and the outer diameter and sides of the holder ring (7) match the diameter and inner surface of the well (2) of the well plate (1) on top of the well (2). 12. The sample holder handling system of claim 11, configured to mate. 16. A specimen holder handling system according to claim 15, wherein said holder ring (7) comprises clamping means for engaging said holder ring (7) with an automatic specimen holder handling system. An insert ring (14) was placed in the bottom (10) of the wells (2) of said well plate (1), said insert ring being inserted into the wells (2) of said well plate (1). 16. Specimen holder handling system according to claim 15, supporting the holder ring (7) of the specimen holder (3). The sample holder (3) comprises a protective container (17), the outer diameter, sides and height of which correspond to the diameter, inner surface and height of the wells (2) of the well plate (1). 12. The specimen holder handling system of claim 11, wherein the specimen holder handling system is configured to mate with.

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